Parathyroid hormone-related protein

Parathyroid hormone-like hormone
PDB rendering based on 1bzg.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1BZG, 1ET3, 1M5N, 3FFD, 3H3G
Identifiers
Symbols	PTHLH ; BDE2; HHM; PLP; PTHR; PTHRP
External IDs	OMIM: 168470 MGI: 97800 HomoloGene: 2113 GeneCards: PTHLH Gene
Gene ontology Molecular function • hormone activity • peptide hormone receptor binding Cellular component • extracellular region • extracellular space • nucleus • nucleolus • cytoplasm • Golgi apparatus Biological process • skeletal system development • endochondral ossification • osteoblast development • adenylate cyclase-activating G-protein coupled receptor signaling pathway • cell-cell signaling • endoderm development • female pregnancy • positive regulation of cell proliferation • negative regulation of cell proliferation • epidermis development • regulation of gene expression • protein processing • positive regulation of cAMP biosynthetic process • epithelial cell differentiation • negative regulation of chondrocyte differentiation • surfactant homeostasis • negative regulation of sequence-specific DNA binding transcription factor activity • cAMP metabolic process • lung alveolus development • mammary gland bud elongation • nipple sheath formation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5744	19227
Ensembl	ENSG00000087494	ENSMUSG00000048776
UniProt	P12272	n/a
RefSeq (mRNA)	NM_002820	NM_008970
RefSeq (protein)	NP_002811	NP_032996
Location (UCSC)	Chr 12: 28.11 – 28.13 Mb	Chr 6: 147.25 – 147.26 Mb
PubMed search

Parathyroid hormone-related protein (or PTHrP) is a protein member of the parathyroid hormone family. It is occasionally secreted by cancer cells (breast cancer, certain types of lung cancer including squamous cell lung carcinoma). However, it also has normal functions.

Function

PTHrP acts as an endocrine, autocrine, paracrine, and intracrine hormone. It regulates endochondral bone development by maintaining the endochondral growth plate at a constant width. It also regulates epithelial-mesenchymal interactions during the formation of the mammary glands.

Tooth eruption

PTHrP is critical in intraosseous phase of tooth eruption where it acts as a signalling molecule to stimulate local bone resorption. Without PTHrP, the bony crypt surrounding the tooth follicle will not resorb, and therefore the tooth will not erupt. In the context of tooth eruption, PTHrP is secreted by the cells of the Reduced Enamel Epithelium.

Mammary glands

It aids in normal mammary gland development.^[1][2] It is necessary for maintenance of the mammary bud. Loss of PTHrP or its receptor causes the mammary bud cell fate to change back into epidermis. In lactation, it may regulate in conjunction with the calcium sensing receptor the mobilization and transfer of calcium to the milk, as well as placental transfer of calcium.

Humoral hypercalcemia of malignancy

PTHrP is related in function to the "normal" parathyroid hormone. When a tumor secretes PTHrP, this can lead to hypercalcemia.^[3] As this is sometimes the first sign of the malignancy, hypercalcemia caused by PTHrP is considered a paraneoplastic phenomenon. PTHR1 is responsible for most cases of humoral hypercalcemia of malignancy.

PTHrP shares the same N-terminal end as parathyroid hormone and therefore it can bind to the same receptor, the Type I PTH receptor (PTHR1). PTHrP can simulate most of the actions of PTH including increases in bone resorption and distal tubular calcium reabsorption, and inhibition of proximal tubular phosphate transport.

However, PTHrP is less likely than PTH to stimulate 1,25-dihydroxyvitamin D production. Therefore, PTHrP does not increase intestinal calcium absorption.

Genetics

Four alternatively spliced transcript variants encoding two distinct isoforms have been observed. There is also evidence for alternative translation initiation from non-AUG (CUG and GUG) start sites, in-frame and downstream of the initiator AUG codon, to give rise to nuclear forms of this hormone.^[4]

Discovery

The protein was first isolated in 1987 by T.J. Martin's team at the University of Melbourne. Miao et al. showed that disruption of the PTHrP gene in mice caused a lethal phenotype and distinct bone abnormalities, suggesting that PTHrP has a physiological function.

Interactions

Parathyroid hormone-related protein has been shown to interact with KPNB1^[5][6] and Arrestin beta 1.^[7]

References

Further reading

PDB gallery 1bzg: THE SOLUTION STRUCTURE OF HUMAN PARATHYROID HORMONE-RELATED PROTEIN (1-34) IN NEAR-PHYSIOLOGICAL SOLUTION, NMR, 30 STRUCTURES  1m5n: Crystal structure of HEAT repeats (1-11) of importin b bound to the non-classical NLS(67-94) of PTHrP

This article incorporates text from the United States National Library of Medicine, which is in the public domain.